Search

Activation of the IL-6 mediated JAK-STAT (Janus associated kinase-signal transducer and activator of transcription) oncogenic signalling plays a major role in hepatocellular carcinoma pathogenesis. The aim of this study is to assess the anti-tumour, anti-proliferative and apoptotic potential of artesunate and its capacity to modulate JAK-STAT pathway in a nitrosodiethylamine mediated experimental hepatocellular carcinoma model. Administration of nitrosodiethylamine (200mg/kg body weight by i.p. Injections) to rats resulted in alterations of liver pathophysiological parameters such as increased relative liver weight, and increased tumour nodule occurrence. It also increased the levels of serum marker enzymes (AST, ALT, ALP, LDH, and γGT) and tumour biomarker (AFP) levels suggestive of its capacity to cause liver tumourigenesis. Additionally, the immunohistochemistry of liver sections pertaining to nitrosodiethylamine administered animals showed increased detection of AgNOR, PCNA, and GST-Pi positive cells suggestive of its capacity to promote liver proliferation associated tumourigenesis. On the contrary, artesunate (25mg/kg bodyweight) supplementation to nitrosodiethylamine administered animals decreased all the above mentioned pathophysiological, biochemical, and immunohistochemistry parameters suggesting its anti-tumour and anti-proliferative potential. Furthermore, immunoblot analysis showed significant up-regulation of IL-6, GP130, JAK-2, STAT-3 (pY705), Bcl-xL, Bcl-2 and simultaneous down-regulation of Caspase-3, PARP and SOCS-3 in nitrosodiethylamine administered animals. Nevertheless, the immunoblot analysis revealed vice-versa on artesunate supplementation to nitrosodiethylamine administered animals, indicating promotion of the feedback loop inhibition mechanism through SOCS3 up-regulation thereby leading to suppression of JAK-STAT signalling. Overall all these findings substantiate that artesunate promotes anti-tumour, anti-proliferation and apoptosis against nitrosodiethylamine mediated hepatocellular carcinoma.

Bacopa monnieri (L.), popularly known as Brahmi, is a revered Ayurvedic medicinal plant used as nerve tonic since time immemorial. The present study aims to investigate the neuroprotective effect of bacosides, the active saponins of Bacopa monnieri (L.) against age associated neurodegeneration and its impact over the prevention of Senile Dementia of Alzheimer's Type (SDAT). The optimum dose of bacosides with no adverse effect was selected by screening its dose dependant activity on ageing biomarker lipofuscin and SDAT biomarker neurotransmitter acetylcholine in the aged female Wistar rat brain. The selected therapeutic dose of bacosides (200 mg/kg) was orally administered for 3 months in middle aged and aged rats and further investigated for its protective action against age associated alterations in neurotransmission system, behavioral paradigms, hippocampal neuronal loss and oxidative stress markers. The results of the present study suggest that bacosides may act as a potential therapeutic intervention in forestalling the deleterious effects of ageing and preventing the age associated pathologies like SDAT.

New Zealand White rabbits, divided into 4 groups were fed with feed containing aflatoxin B(1) (AFB(1)) @ 0.5 ppm (group I), ochratoxin A (OA) @ 1 ppm (group II), AFB(1) and OA @ 0.5 ppm and 1 ppm, respectively (group III) and standard feed (group IV) for 60 days. Mortality and decrease in body weight were highest in the interaction group. Superoxide dismutase, catalase and malondialdehyde levels were increased in all the toxin fed groups with maximum elevation in group III. Significant decrease in the antibody titre to sRBC was observed in groups I and II. Significant reduction of HI and CMI responses was observed in group III. Grossly, liver was the most affected organ in AFB(1) treated animals. Microscopically, vacuolar degeneration of hepatocytes, bile duct epithelial hyperplasia and hypertrophy and peribiliary fibrosis were consistently observed. Ultrastructurally, hepatocytes revealed varying degrees of degeneration, swollen endoplasmic reticulum and pleomorphism of mitochondria. OA produced significant nephrotoxicity with the pale, soft and enlarged kidneys showing discoloured foci over the surface. Microscopically, kidneys revealed degeneration of the proximal convoluted tubules and the testes were atrophic. Ultrastructurally, disruption of the mitochondrial membrane and swelling of the endoplasmic reticulum were observed. In group III, gross and histopathological changes were observed both in liver and kidneys and were of greater severity as compared to those of groups I and II. Ultrastructurally, hepatocytes revealed nuclear distortion, marginated heterochromatin, chromatolysis, electron opaque mitochondria with vacuolations and disarray of cristae and loss of cytoplasmic organelles. The results suggested an additive interaction of AFB(1) and OA in rabbits.